Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is classified according to cause into nociceptive pain, neuropathic pain and psychogenic pain. As pain caused by an unknown cause, fibromyalgia syndrome is known.
Neuropathic pain is pathological pain caused by peripheral or central nervous system dysfunction, more specifically, pain caused by e.g., direct damage and oppression of the nerve tissue despite of no nociceptive stimulus to a nociceptor. As an therapeutic agent for neuropathic pain, an anticonvulsant, an antidepressant, an anxiolytic drug or an antiepileptic drug (gabapentin, pregabalin or the like) is used.
Fibromyalgia syndrome is a disorder in which systemic pain is the leading symptom and neuropsychiatric and neurovegetative symptoms are the secondary symptoms. As the therapeutic agents for fibromyalgia syndrome, pregabalin, which has been approved in the United States and Japan, duloxetine and milnacipran, which have been approved in the United States, are principally used. Also, drugs which are not approved as a therapeutic agent for fibromyalgia syndrome, i.e., a nonsteroidal anti-inflammatory agent, an opioid compound, an antidepressant, an anticonvulsant and an antiepileptic drug are used. However, nonsteroidal anti-inflammatory agents and opioid compounds are generally said to have a low therapeutic effect (FR 2 567 885).
FR '885 discloses that substituted piperidines have a cardiotonic activity. JP 2006-008664 discloses that imidazole derivatives have an FXa inhibitory effect. WO 2003/031432 suggests that substituted piperidines have a potential drug efficacy against overweight or obesity. WO 2013/147160 discloses that an imidazole derivative has an analgesic action.
However, therapy with a conventional therapeutic agent for neuropathic pain is highly frequently associated with central nervous system adverse effects (e.g., dizziness, nausea or vomiting). To enable long-term administration, development of a novel therapeutic agent for neuropathic pain has been desired.
Even pregabalin, duloxetine and milnacipran, which have been approved as therapeutic agents for fibromyalgia syndrome, fail to provide clinically satisfactory therapeutic effect against fibromyalgia syndrome and their drug efficacy significantly varies among patients. In that context, it has been strongly desired to develop a novel therapeutic agent for fibromyalgia syndrome having a strong pharmacological activity and exerting a therapeutic effect on a wide variety of patients.
FR '885 suggests that the substituted piperidines described therein have an efficacy for migraine and WO '160 discloses that the imidazole derivative described therein has an analgesic action. However, neither disclosure of the compound itself having an analgesic action nor suggestion on the relevancy of an analgesic action to a chemical structure is provided. JP '664 which describes imidazole derivatives and WO '432 which describes substituted piperidines neither disclose nor suggest potentiality of analgesic action that these compounds have.
Under the circumstances, it could be helpful to provide a compound having an analgesic action for pain, in particular, neuropathic pain and/or fibromyalgia syndrome.